Measurable outcomes of consumer engagement in health research: A scoping review.

Background: Consumer engagement is increasingly recognized as an instrumental component of health research, with many institutions and international bodies mandating it as part of the research and funding process. Given an increasing utilization of consumer engagement in health research, it is critical to identify the literature which support its value and tools that capture successful outcomes. To develop an overview of the literature, we conducted an umbrella scoping review exploring important outcomes of consumer engagement in health research combined with a scoping review of relevant frameworks. Specifically, we aimed to capture outcomes which reflect authentic and meaningful consumer engagement. Methods: Four databases (PubMed, Embase, CINAHL and Cochrane Library) were searched using key search terms. Records were included if they were review articles or frameworks that addressed outcomes of consumer engagement in health research. Data was analyzed using descriptive statistics and an inductive qualitative content analysis. Identified outcomes were sorted based on the three most relevant stakeholder groups (consumer, researcher, institution). Results: A total of twenty articles that explored a variety of health disciplines were included. We identified fifteen measurable outcomes of consumer engagement in health research. Eight core outcomes were relevant to all stakeholder groups, and were considered fundamental to authentic consumer engagement including (1) trust, (2) empowerment, (3) respect, (4) confidence in the outcomes of the research, (5) transparency of the research process, (6) satisfaction with the consumer engagement program, (7) knowledge and experiences of consumers, and (8) degree of consumer engagement. Outcomes pertaining to specific stakeholder groups included representativeness and diversity of the consumer groups, research relevance to consumers, funding opportunities, quality/validity of the research, recruitment/retention rates, translation and dissemination of research, and interpretation of results. Conclusion: This review identified key measurable outcomes that could be captured when evaluating the impacts of consumer engagement on health research and the success of consumer engagement programs. All outcomes identified were relatively underexplored within the literature, and inadequately and/or inconsistently evaluated amongst studies. Future research should consult all stakeholder groups to identify outcomes perceived to be reflective of optimal consumer engagement.

Representativeness of the PDOPPS cohort compared to the Australian PD population.

BACKGROUND: The Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS) is an international, prospective study following persons treated by peritoneal dialysis (PD) to identify modifiable practices associated with improvements in PD technique and person survival. The aim of this study was to assess the representativeness of the Australian cohort included in PDOPPS compared to the complete Australian PD population, as reported to the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry. METHODS: Adults with at least one PD treatment reported to ANZDATA Registry during the census period of PDOPPS Phase I (November 2014 to April 2018) were compared to the Australian PDOPPS cohort. The primary outcomes were the representativeness of centres and persons. Secondary outcomes explored the association of person characteristics with consent to study participation. RESULTS: After data linkage, 511 PDOPPS participants were compared to 5616 Australians treated with PD. Within centres eligible for PDOPPS, selected centres were similar to other Australian centres. The PDOPPS participants' cohort tended to include older persons, more males, a higher proportion of Caucasians and more persons with higher socioeconomic advantage compared to the Australian PD population. Differences in distribution across sex and ethnicities between the PDOPPS cohort and the overall PD population were in part due to the selection and consent processes, during which females and non-Caucasians were more likely to not consent to PDOPPS participation. CONCLUSION: Sampling methods used in PDOPPS allowed for good national representativeness of the included centres. However, representativeness of the unweighted PDOPPS sample was suboptimal in regard to some participant characteristics.

Conducting clinical trials during the COVID-19 pandemic-a collaborative trial network response.

The unprecedented demand placed on healthcare systems from the COVID-19 pandemic has forced a reassessment of clinical trial conduct and feasibility. Consequently, the Australasian Kidney Trials Network (AKTN), an established collaborative research group known for conducting investigator-initiated global clinical trials, had to efficiently respond and adapt to the changing landscape during COVID-19. Key priorities included ensuring patient and staff safety, trial integrity and network sustainability for the kidney care community. New resources have been developed to enable a structured review and contingency plan of trial activities during the pandemic and beyond.

A Randomized Trial on the Effect of Phosphate Reduction on Vascular End Points in CKD (IMPROVE-CKD).

BACKGROUND: Hyperphosphatemia is associated with increased fibroblast growth factor 23 (FGF23), arterial calcification, and cardiovascular mortality. Effects of phosphate-lowering medication on vascular calcification and arterial stiffness in CKD remain uncertain. METHODS: To assess the effects of non-calcium-based phosphate binders on intermediate cardiovascular markers, we conducted a multicenter, double-blind trial, randomizing 278 participants with stage 3b or 4 CKD and serum phosphate >1.00 mmol/L (3.10 mg/dl) to 500 mg lanthanum carbonate or matched placebo thrice daily for 96 weeks. We analyzed the primary outcome, carotid-femoral pulse wave velocity, using a linear mixed effects model for repeated measures. Secondary outcomes included abdominal aortic calcification and serum and urine markers of mineral metabolism. RESULTS: A total of 138 participants received lanthanum and 140 received placebo (mean age 63.1 years; 69% male, 64% White). Mean eGFR was 26.6 ml/min per 1.73 m2; 45% of participants had diabetes and 32% had cardiovascular disease. Mean serum phosphate was 1.25 mmol/L (3.87 mg/dl), mean pulse wave velocity was 10.8 m/s, and 81.3% had abdominal aortic calcification at baseline. At 96 weeks, pulse wave velocity did not differ significantly between groups, nor did abdominal aortic calcification, serum phosphate, parathyroid hormone, FGF23, and 24-hour urinary phosphate. Serious adverse events occurred in 63 (46%) participants prescribed lanthanum and 66 (47%) prescribed placebo. Although recruitment to target was not achieved, additional analysis suggested this was unlikely to have significantly affected the principle findings. CONCLUSIONS: In patients with stage 3b/4 CKD, treatment with lanthanum over 96 weeks did not affect arterial stiffness or aortic calcification compared with placebo. These findings do not support the role of intestinal phosphate binders to reduce cardiovascular risk in patients with CKD who have normophosphatemia. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Australian Clinical Trials Registry, ACTRN12610000650099.

Effects of Allopurinol on the Progression of Chronic Kidney Disease.

BACKGROUND: Elevated serum urate levels are associated with progression of chronic kidney disease. Whether urate-lowering treatment with allopurinol can attenuate the decline of the estimated glomerular filtration rate (eGFR) in patients with chronic kidney disease who are at risk for progression is not known. METHODS: In this randomized, controlled trial, we randomly assigned adults with stage 3 or 4 chronic kidney disease and no history of gout who had a urinary albumin:creatinine ratio of 265 or higher (with albumin measured in milligrams and creatinine in grams) or an eGFR decrease of at least 3.0 ml per minute per 1.73 m2 of body-surface area in the preceding year to receive allopurinol (100 to 300 mg daily) or placebo. The primary outcome was the change in eGFR from randomization to week 104, calculated with the Chronic Kidney Disease Epidemiology Collaboration creatinine equation. RESULTS: Enrollment was stopped because of slow recruitment after 369 of 620 intended patients were randomly assigned to receive allopurinol (185 patients) or placebo (184 patients). Three patients per group withdrew immediately after randomization. The remaining 363 patients (mean eGFR, 31.7 ml per minute per 1.73 m2; median urine albumin:creatinine ratio, 716.9; mean serum urate level, 8.2 mg per deciliter) were included in the assessment of the primary outcome. The change in eGFR did not differ significantly between the allopurinol group and the placebo group (-3.33 ml per minute per 1.73 m2 per year [95% confidence interval {CI}, -4.11 to -2.55] and -3.23 ml per minute per 1.73 m2 per year [95% CI, -3.98 to -2.47], respectively; mean difference, -0.10 ml per minute per 1.73 m2 per year [95% CI, -1.18 to 0.97]; P = 0.85). Serious adverse events were reported in 84 of 182 patients (46%) in the allopurinol group and in 79 of 181 patients (44%) in the placebo group. CONCLUSIONS: In patients with chronic kidney disease and a high risk of progression, urate-lowering treatment with allopurinol did not slow the decline in eGFR as compared with placebo. (Funded by the National Health and Medical Research Council of Australia and the Health Research Council of New Zealand; CKD-FIX Australian New Zealand Clinical Trials Registry number, ACTRN12611000791932.).

Study Protocol for Better Evidence for Selecting Transplant Fluids (BEST-Fluids): a pragmatic, registry-based, multi-center, double-blind, randomized controlled trial evaluating the effect of intravenous fluid therapy with Plasma-Lyte 148 versus 0.9% saline on delayed graft function in deceased donor kidney transplantation.

BACKGROUND: Delayed graft function, the requirement for dialysis due to poor kidney function post-transplant, is a frequent complication of deceased donor kidney transplantation and is associated with inferior outcomes and higher costs. Intravenous fluids given during and after transplantation may affect the risk of poor kidney function after transplant. The most commonly used fluid, isotonic sodium chloride (0.9% saline), contains a high chloride concentration, which may be associated with acute kidney injury, and could increase the risk of delayed graft function. Whether using a balanced, low-chloride fluid instead of 0.9% saline is safe and improves kidney function after deceased donor kidney transplantation is unknown. METHODS: BEST-Fluids is an investigator-initiated, pragmatic, registry-based, multi-center, double-blind, randomized controlled trial. The primary objective is to compare the effect of intravenous Plasma-Lyte 148 (Plasmalyte), a balanced, low-chloride solution, with the effect of 0.9% saline on the incidence of delayed graft function in deceased donor kidney transplant recipients. From January 2018 onwards, 800 participants admitted for deceased donor kidney transplantation will be recruited over 3 years in Australia and New Zealand. Participants are randomized 1:1 to either intravenous Plasmalyte or 0.9% saline peri-operatively and until 48 h post-transplant, or until fluid is no longer required; whichever comes first. Follow up is for 1 year. The primary outcome is the incidence of delayed graft function, defined as dialysis in the first 7 days post-transplant. Secondary outcomes include early kidney transplant function (composite of dialysis duration and rate of improvement in graft function when dialysis is not required), hyperkalemia, mortality, graft survival, graft function, quality of life, healthcare resource use, and cost-effectiveness. Participants are enrolled, randomized, and followed up using the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry. DISCUSSION: If using Plasmalyte instead of 0.9% saline is effective at reducing delayed graft function and improves other clinical outcomes in deceased donor kidney transplantation, this simple, inexpensive change to using a balanced low-chloride intravenous fluid at the time of transplantation could be easily implemented in the vast majority of transplant settings worldwide. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12617000358347. Registered on 8 March 2017. ClinicalTrials.gov: NCT03829488. Registered on 4 February 2019.

Practice of Peritoneal Dialysis Catheter Flushing in Australia and New Zealand: Multi-Center Cross-Sectional Survey.

BACKGROUND: Evidence of effective interventions to prevent peritoneal dialysis (PD) catheter malfunction before first use is presently insufficient to guide clinical care. Regular flushing of the PD catheter (e.g. before PD commencement) has been adopted by some practitioners in the belief that it will prevent catheter obstruction and/or malfunction. The aim of this study was to characterize and evaluate PD catheter flushing practices across Australian and New Zealand PD units. METHODS: An on-line survey was distributed to all 62 PD units in Australia (12 August 2016; n = 51) and New Zealand (2 February 2017; n = 11), with questions relating to PD catheter flushing practices, audit, and outcomes. RESULTS: Forty-nine units of variable size (< 16 to > 100 patients) completed the survey (79% response rate). All centers flushed PD catheters at some stage after insertion as routine unit practice. Forty-one units (84%) routinely flushed during periods of PD rest at varying intervals ranging from alternate daily to monthly. The type and volume of solution used to flush varied between units. Units that practised routine flushing of PD catheters were almost twice as likely to audit their catheter-related outcomes (66% vs 38%, p = 0.23) and more likely to have reported blocked catheters in the preceding 12 months (84% vs 0%, p = 0.01) compared with those units that did not routinely flush PD catheters. Thirty units (61%) regularly audited and monitored catheter-related outcomes. CONCLUSIONS: This study identified a wide variation in center practices relating to PD catheter flushing. Drawing conclusions about any relationship between flushing practices and clinical outcomes was impeded by the relatively low uptake of regular auditing and monitoring of catheter-related outcomes across surveyed units. Evaluation of the benefits and harms of standardized PD catheter flushing practices on patient outcomes in a randomized trial is needed to guide practice.

Azithromycin for Acute Exacerbations of Asthma : The AZALEA Randomized Clinical Trial.

Importance: Guidelines recommend against antibiotic use to treat asthma attacks. A study with telithromycin reported benefit, but adverse reactions limit its use. Objective: To determine whether azithromycin added to standard care for asthma attacks in adults results in clinical benefit. Design, Setting, and Participants: The Azithromycin Against Placebo in Exacerbations of Asthma (AZALEA) randomized, double-blind, placebo-controlled clinical trial, a United Kingdom-based multicenter study in adults requesting emergency care for acute asthma exacerbations, ran from September 2011 to April 2014. Adults with a history of asthma for more than 6 months were recruited within 48 hours of presentation to medical care with an acute deterioration in asthma control requiring a course of oral and/or systemic corticosteroids. Interventions: Azithromycin 500 mg daily or matched placebo for 3 days. Main Outcomes and Measures: The primary outcome was diary card symptom score 10 days after randomization, with a hypothesized treatment effect size of -0.3. Secondary outcomes were diary card symptom score, quality-of-life questionnaires, and lung function changes, all between exacerbation and day 10, and time to a 50% reduction in symptom score. Results: Of 4582 patients screened at 31 centers, 199 of a planned 380 were randomized within 48 hours of presentation. The major reason for nonrecruitment was receipt of antibiotics (2044 [44.6%] screened patients). Median time from presentation to drug administration was 22 hours (interquartile range, 14-28 hours). Exacerbation characteristics were well balanced across treatment arms and centers. The primary outcome asthma symptom scores were mean (SD), 4.14 (1.38) at exacerbation and 2.09 (1.71) at 10 days for the azithromycin group and 4.18 (1.48) and 2.20 (1.51) for the placebo group, respectively. Using multilevel modeling, there was no significant difference in symptom scores between azithromycin and placebo at day 10 (difference, -0.166; 95% CI, -0.670 to 0.337), nor on any day between exacerbation and day 10. No significant between-group differences were observed in quality-of-life questionnaires or lung function between exacerbation and day 10, or in time to 50% reduction in symptom score. Conclusions and Relevance: In this randomized population, azithromycin treatment resulted in no statistically or clinically significant benefit. For each patient randomized, more than 10 were excluded because they had already received antibiotics. Trial Registration: clinicaltrials.gov Identifier: NCT01444469.

Endocrine therapy, new biologicals, and new study designs for presurgical studies in breast cancer.

The preoperative setting is increasingly popular for the clinical investigation of hormonal agents and new biological drugs. The effectiveness of endocrine agents is well established for estrogen receptor-positive disease, and the emphasis in preoperative studies is on their combination with agents targeted at resistance mechanisms over 3 or more months. New agents are also being assessed for early evidence of clinical efficacy in shorter-term window-of-opportunity studies. The establishment of Ki67 as an intermediate marker of treatment benefit and of long-term outcome, with endocrine drugs, provides the opportunity for new trial designs with Ki67 as the primary endpoint. The PeriOperative Endocrine Therapy for Individualizing Care (POETIC) trial is randomizing (2:1) 4000 estrogen receptor-positive patients to 2 weeks presurgical treatment with a nonsteroidal aromatase inhibitor or no presurgical treatment. It provides a unique opportunity for detailed study of the determinants of response and resistance to estrogen deprivation as well as testing the role of presurgical therapy for improved biomarker-based estimates of prognosis.

An organizational guide for an effective developmental program in the NICU.

Many newborn intensive care units have put a great deal of energy and resources into their efforts to provide developmentally supportive care. Yet, without consistent leadership and clear accountabilities, developmental care will depend on the individual philosophy, or even the mood, of the health care professional at the bedside. Under these circumstances, infants and families experience an unpredictable and inconsistent quality of care. This article presents a guide to assist nurseries in structuring successful programs of developmentally supportive, family-centered care through well-described accountabilities that translate into consistent, high-quality care for infants and families in the NICU.